London School of Hygiene & Tropical Medicine

A drug given to pregnant women in 35 countries worldwide to protect against malaria has been shown also to safeguard against the consequences of gonorrhoea, chlamydia, trichomoniasis, and bacterial vaginosis, according to a new study published in Clinical Infectious Diseases. 

The World Health Organization recommends providing intermittent preventive treatment (IPTp) using sulphadoxine-pyrimethamine (SP) to pregnant women living in malaria-endemic areas as part of every scheduled antenatal care visit, from the second trimester until delivery, to reduce adverse birth outcomes caused by malaria infection.

This study has produced the first compelling evidence that the same preventive treatment reduces adverse birth outcomes attributable to curable sexually transmitted/reproductive tract infections (STIs/RTIs).

The research, led by the London School of Hygiene & Tropical Medicine with partners the University of Zambia, involved 1,086 pregnant women in Zambia. Researchers investigated the protective effect that different doses of IPTp-SP had on pregnancy outcomes. The analyses confirmed IPTp-SP protects against adverse birth outcomes but of particular interest to the team was the effect the drug had on the infections themselves.

At delivery, women who experienced an adverse birth outcome who had had two or more doses of IPTp-SP compared to 0-1 dose were 76% less likely to have a malaria infection, 94% less likely to have gonorrhoea or chlamydia, and 66% less likely to have trichomoniasis or bacterial vaginosis. 

There are 880,000 stillbirths and 1.2 million newborn deaths each year in sub-Saharan Africa, many of which are linked to maternal infection. A 2012 School study found that nearly 4 of every 10 women at health facilities have a malaria infection. An even higher number of women, if added together, are infected with the STIs/RTIs syphilis, gonorrhoea, chlamydia, tichomononiasis and bacterial vaginosis.

Lead author of this new study, Assistant Professor Matthew Chico from the London School of Hygiene & Tropical Medicine, said: "Sexually transmitted and reproductive tract infections are linked to devastating birth consequences for pregnant women, including spontaneous abortion, stillbirth and premature and low birthweight. While sulfadoxine-pyrimethamine has been thought to offer pregnant women protection against other infections, no evidence existed - until now. The findings show that IPTp-SP offers unrecognised potential that extends beyond its life-saving protection against malaria."

In the trial, researchers worked backwards to categorise women according to the number of doses of IPTp-SP each had received during the antenatal period.  Retrospective laboratory analyses confirmed that infections at enrolment, unknown to investigators and women, were equally prevalent across the treatment groups. 

Women who went on to receive two or more IPTp-SP doses compared to 0-1 dose had their odds of experiencing any adverse birth outcome (stillbirth, low birthweight, preterm delivery or intrauterine growth retardation) reduced by 45%, and 13% further with three or more doses. Two doses of IPTp-SP, compared to 0-1, reduced the incidence of preterm delivery by 58%, and 21% further if women received three or more doses.

Conducted in rural Zambia, all pregnant women in the trial received antenatal care according to national policies that included the provision of IPTp-SP, testing for syphilis and HIV. However, screening is not routine for gonorrhoea, chlamydia, trichomoniasis and bacterial vaginosis. The same is true in high-income countries.

In low-income countries healthcare providers manage curable STIs/RTIs using diagnostic and treatment algorithms, a method that is useful among men for whom these infections are most often symptomatic. However, these same infections in women are most often asymptomatic and are therefore rarely diagnosed and treated. 

Matthew Chico said: "Our study helps to explain why IPTp-SP continues to protect pregnant women against adverse birth outcomes in areas where malaria transmission is extremely low. Interestingly, women with neither a malaria infection nor any of the sexually transmitted and reproductive tract infections we examined, and who received two or more doses of IPTp-SP, had 73% fewer adverse birth outcomes than women given 0-1 dose." 

The authors hope that these results will serve as a catalyst for scaling-up coverage of preventive treatment. Currently only 24% of pregnant women in sub-Saharan Africa receive two SP doses, well below national and international targets. 

Matthew Chico added: "Sulphadoxine-pyrimethamine is a cheap 'double protection' drug - 20 US cents per dose. For that bargain price, pregnant women receive broad protection against a range of infections which can lead to very serious consequences. It's almost public health malpractice not to provide IPTp-SP in areas where it is policy. Policymakers and healthcare officials need to recognise the full benefits of IPTp-SP and ensure pregnant women in sub-Saharan Africa receive three or more doses."

The researchers acknowledge that this was an observational study so the results only reflect associations between IPTp-SP doses and birth outcomes and infections.  However, these findings demonstrate a clear dose-response relationship and are biologically plausible, adding to the confidence held by the researchers. Additional research, including longitudinal studies, are needed to confirm the impact of IPTp-SP on adverse birth outcomes and infections.

Publication

Matthew Chico, Enesia Banda Chaponda, Cono Ariti, Daniel Chandramohan. Sulfadoxine-Pyrimethamine Exhibits Dose-Response Protection Against Adverse Birth Outcomes Related to Sexually Transmitted and Reproductive Tract Infections. Clinical Infectious Diseases. DOI:10.1093/cid/cix026